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Dissecting gene activation and chromatin remodeling dynamics in single human cells undergoing reprogramming.
Martinez-Sarmiento, Jose A; Cosma, Maria Pia; Lakadamyali, Melike.
Afiliación
  • Martinez-Sarmiento JA; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
  • Cosma MP; Center for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain; ICREA, 08010 Barcelona, Spain; Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 510080 Guangzhou, China. Electronic address: pia.cosma@crg.eu.
  • Lakadamyali M; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: melikel@pennmedicine.upenn.edu.
Cell Rep ; 43(5): 114170, 2024 May 28.
Article en En | MEDLINE | ID: mdl-38700983
ABSTRACT
During cell fate transitions, cells remodel their transcriptome, chromatin, and epigenome; however, it has been difficult to determine the temporal dynamics and cause-effect relationship between these changes at the single-cell level. Here, we employ the heterokaryon-mediated reprogramming system as a single-cell model to dissect key temporal events during early stages of pluripotency conversion using super-resolution imaging. We reveal that, following heterokaryon formation, the somatic nucleus undergoes global chromatin decompaction and removal of repressive histone modifications H3K9me3 and H3K27me3 without acquisition of active modifications H3K4me3 and H3K9ac. The pluripotency gene OCT4 (POU5F1) shows nascent and mature RNA transcription within the first 24 h after cell fusion without requiring an initial open chromatin configuration at its locus. NANOG, conversely, has significant nascent RNA transcription only at 48 h after cell fusion but, strikingly, exhibits genomic reopening early on. These findings suggest that the temporal relationship between chromatin compaction and gene activation during cellular reprogramming is gene context dependent.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Histonas / Ensamble y Desensamble de Cromatina / Reprogramación Celular Límite: Humans Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Histonas / Ensamble y Desensamble de Cromatina / Reprogramación Celular Límite: Humans Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos